As with other ion channels, the activity of BK splice variants is controlled in part by kinases and phosphatases [15,70–73]. Recent studies have made clear how post-translational modifications such as phosphorylation/dephosphorylation can control the response to alcohol [74–77], as well as provide a potentially elegant mechanism for tolerance. Thus, a recent study demonstrated that the calcium/calmodulin-dependent protein kinase, CaMKII, is crucial in the effects of alcohol on the BK channel α subunit. Incremental CaMKII-mediated phosphorylation of Thr107 in the BK tetramer progressively increased channel activity and gradually switched the channel alcohol response from robust activation to inhibition. Thus, CaMKII phosphorylation of slo Thr107 works as a ‘molecular dimmer switch’ that could mediate tolerance to alcohol [26].
